This work analyzed the feasibility of pre-treatments to improve the anaerobic digestion (AD) of waste activated sludge (WAS) at 20 degrees C. We investigated different physicochemical pre-treatments (thermal at 115 degrees C, thermo-alkaline at pH 10 and 70 degrees C and ozonation at 190 mg-O-3 L-1) by comparing their performances about COD solubilization and sludge disintegration rate. Best performances were obtained by thermo-alkaline pre-treatment, followed by thermal and ozonation; results were consistent with literature. Pre-treated WAS was fed to 12 1-L anaerobic digesters operated in semi-continuous mode. Thermal and thermo-alkaline reactors produced biogas yields (0.30-0.36 m(3) kg(-1) VS in standard conditions, 65-70 % methane) analogous to mesophilic conditions. The economic assessment of the scale-up of the whole process demonstrated that thermo-alkaline pre-treatment made AD at 20 degrees C economically profitable for WAS generated by a 20,000 PE WWTP. (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.